Key result
High-risk clinical phenotype linked to ~72% higher MACE risk in asymptomatic LV systolic dysfunction.
Why the study?
LVSD is heterogeneous with multiple factors influencing prognosis, and better phenotyping of asymptomatic individuals is needed to inform preventative strategies.
Cohort (n=1,563)
Hazard Ratio: 1.72 (95% CI 1.36–2.35)
Absolute Event Rate: 29.56% vs 15.23%
p-value: p=<0.001
Clustering of clinical variables in asymptomatic individuals with LVSD identifies distinct risk profiles that predict future MACE and heart failure, independent of LVEF.
Should not yet guide risk stratification in asymptomatic LVSD; hypothesis-generating for clinical phenotyping to refine MACE prediction beyond LVEF.
AIMS: Left ventricular systolic dysfunction (LSVD) is a heterogeneous condition with several factors influencing prognosis. Better phenotyping of asymptomatic individuals can inform preventative strategies. This study aims to explore the clinical phenotypes of LVSD in initially asymptomatic subjects and their association with clinical outcomes and cardiovascular abnormalities through multi-dimensional data clustering. METHODS AND RESULTS: Clustering analysis was performed on 60 clinically available variables from 1563 UK Biobank participants without pre-existing heart failure (HF) and with left ventricular ejection fraction (LVEF) < 50% on cardiovascular magnetic resonance (CMR) assessment. Risks of developing HF, other cardiovascular events, death, and a composite of major adverse cardiovascular events (MACE) associated with clusters were investigated. Cardiovascular imaging characteristics, not included in the clustering analysis, were also evaluated. Three distinct clusters were identified, differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles. A stepwise increase in risk profile was observed from Cluster 1 to Cluster 3, independent of traditional risk factors and LVEF. Compared with Cluster 1, the lowest risk subset, the risk of MACE ranged from 1.42 [95% confidence interval (CI): 1.03-1.96; P < 0.05] for Cluster 2 to 1.72 (95% CI: 1.36-2.35; P < 0.001) for Cluster 3. Cluster 3, the highest risk profile, had features of adverse cardiovascular imaging with the greatest LV re-modelling, myocardial dysfunction, and decrease in arterial compliance. CONCLUSIONS: Clustering of clinical variables identified three distinct risk profiles and clinical trajectories of LVSD amongst initially asymptomatic subjects. Improved characterization may facilitate tailored interventions based on the LVSD sub-type and improve clinical outcomes.
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Rauseo et al. (2023) conducted a cohort in Asymptomatic left ventricular systolic dysfunction (LVSD) (n=1,563). High-risk clinical phenotype (Cluster 3) vs. Low-risk clinical phenotype (Cluster 1) was evaluated on Major adverse cardiovascular events (MACE), a composite of heart failure, other cardiovascular events, or cardiovascular death (HR 1.72, 95% CI 1.36-2.35, p=<0.001). In initially asymptomatic individuals with left ventricular systolic dysfunction, a high-risk clinical phenotype cluster was associated with an increased risk of major adverse cardiovascular events compared to a low-risk cluster (HR 1.72).
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